Managing Semaglutide Side Effects For Weight Loss

Weight Loss Medication Administration

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Key Points Question Are glucagon-like peptide-1 receptor agonists semaglutide and liraglutide, which were originally introduced for the treatment of type 2 diabetes and are frequently prescribed due to their weight loss properties, associated with disproportionately increased reporting of suicidality? Findings This disproportionality analysis through the case-control design based on the World Health Organization global database collecting suspected adverse drug reactions, identified a disproportionality signal of suicidal ideation with semaglutide, which remained significant when comparing semaglutide with dapagliflozin and metformin and in the subgroup of patients with coreported use of antidepressants and benzodiazepines. Meaning A detected signal of semaglutide-associated suicidal ideation warrants urgent clarification. Abstract Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern. Objectives To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide. Design, Setting, and Participants Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023. Exposure Treatment with semaglutide or liraglutide regardless of indication or treatment duration. Main Outcomes and Measures Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively. Results A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95). Conclusions and Relevance This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.

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Unlocking the Power of Ketosis

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Managing Semaglutide Side Effects For Weight Loss

The Benefits of Shark Tank Keto Max

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FAQ

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